Mechanism of homodimeric cytokine receptor activation and dysregulation by oncogenic mutations
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- Stephan Wilmes
- Department of Biology and Center of Cellular Nanoanalytics, University of Osnabrück, 49076 Osnabrück, Germany.
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- Maximillian Hafer
- Department of Biology and Center of Cellular Nanoanalytics, University of Osnabrück, 49076 Osnabrück, Germany.
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- Joni Vuorio
- Department of Physics, University of Helsinki, Helsinki, Finland.
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- Julie A. Tucker
- York Biomedical Research Institute and Department of Biology, University of York, Heslington, York YO10 5DD, UK.
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- Hauke Winkelmann
- Department of Biology and Center of Cellular Nanoanalytics, University of Osnabrück, 49076 Osnabrück, Germany.
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- Sara Löchte
- Department of Biology and Center of Cellular Nanoanalytics, University of Osnabrück, 49076 Osnabrück, Germany.
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- Tess A. Stanly
- York Biomedical Research Institute and Department of Biology, University of York, Heslington, York YO10 5DD, UK.
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- Katiuska D. Pulgar Prieto
- York Biomedical Research Institute and Department of Biology, University of York, Heslington, York YO10 5DD, UK.
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- Chetan Poojari
- Department of Physics, University of Helsinki, Helsinki, Finland.
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- Vivek Sharma
- Department of Physics, University of Helsinki, Helsinki, Finland.
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- Christian P. Richter
- Department of Biology and Center of Cellular Nanoanalytics, University of Osnabrück, 49076 Osnabrück, Germany.
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- Rainer Kurre
- Department of Biology and Center of Cellular Nanoanalytics, University of Osnabrück, 49076 Osnabrück, Germany.
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- Stevan R. Hubbard
- Skirball Institute and Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY, USA.
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- K. Christopher Garcia
- Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA, USA.
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- Ignacio Moraga
- Division of Cell Signalling and Immunology, School of Life Sciences, University of Dundee, Dundee, UK.
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- Ilpo Vattulainen
- Department of Physics, University of Helsinki, Helsinki, Finland.
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- Ian S. Hitchcock
- York Biomedical Research Institute and Department of Biology, University of York, Heslington, York YO10 5DD, UK.
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- Jacob Piehler
- Department of Biology and Center of Cellular Nanoanalytics, University of Osnabrück, 49076 Osnabrück, Germany.
説明
<jats:title>Activated by interaction</jats:title> <jats:p> Cytokines trigger immune responses when they bind to their cognate receptors. Class I cytokine receptors rely on the associated Janus kinase 2 (JAK2) to initiate signal transduction. There has been debate over whether activation involves ligand-induced dimerization of these receptors or ligand-induced conformational change of preformed dimers. Wilmes <jats:italic>et al.</jats:italic> imaged cytokine receptors in the plasma membranes of live human cells by single-molecule fluorescence microscopy and observed ligand-induced dimerization. They found that the JAK2 pseudokinase domains contribute to dimerization and that hyperactive JAK2 mutants promote dimerization, consistent with the model that dimerization triggers activation. </jats:p> <jats:p> <jats:italic>Science</jats:italic> , this issue p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6478" page="643" related-article-type="in-this-issue" vol="367" xlink:href="10.1126/science.aaw3242">643</jats:related-article> </jats:p>
収録刊行物
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- Science
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Science 367 (6478), 643-652, 2020-02-07
American Association for the Advancement of Science (AAAS)